2. Academic Validation
  3. VPS34-IN1 induces apoptosis of ER + breast cancer cells via activating PERK/ATF4/CHOP pathway

VPS34-IN1 induces apoptosis of ER + breast cancer cells via activating PERK/ATF4/CHOP pathway

  • Biochem Pharmacol. 2023 Jun 6;115634. doi: 10.1016/j.bcp.2023.115634.
Qiuya Wu 1,  Duanfang Zhou 1,  Zhengze Shen 2,  Bo Chen 1,  Gang Wang 1,  Lihong Wu 1,  Limei Zhang 1,  Xiaoli Li 3,  Lie Yuan 1,  Yuanli Wu 1,  Na Qu 1,  Weiying Zhou 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing 400016, China.
  • 2 Department of Pharmacy, Yongchuan Hospital of Chongqing Medical University, 439 Xuanhua Road, Yongchuan District, Chongqing 402160, China.
  • 3 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing 400016, China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing 400016, China.
  • 4 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing 400016, China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing 400016, China. Electronic address: wyzhou0118@cqmu.edu.cn.
PMID: 37290596 DOI: 10.1016/j.bcp.2023.115634
Abstract

VPS34-IN1 is a specific selective inhibitor of Class III Phosphatidylinositol 3-kinase (PI3K) and has been shown to exhibit a significant antitumor effect in leukemia and liver Cancer. In current study, we focused on the Anticancer effect and potential mechanism of VPS34-IN1 in Estrogen Receptor positive (ER + ) breast Cancer. Our results revealed that VPS34-IN1 inhibited the viability of ER + breast Cancer cells in vitro and in vivo. Flow cytometry and western blot analyses showed that VPS34-IN1 treatment induced breast Cancer cell apopotosis. Interestingly, VPS34-IN1 treatment activated protein kinase R (PKR)-like ER kinase (PERK) branch of endoplasmic reticulum (ER) stress. Furthermore, knockdown of PERK by siRNA or inhibition of PERK activity by chemical inhibitor GSK2656157 could attenuate VPS34-IN1-mediated Apoptosis in ER + breast Cancer cells. Collectively, VPS34-IN1 has an antitumor effect in breast Cancer, and it may result from activating PERK/ATF4/CHOP pathway of ER stress to induce cell Apoptosis. These findings broaden our understanding of the anti-breast Cancer effects and mechanisms of VPS34-IN1 and provide new ideas and reference directions for the treatment of ER + breast Cancer.

Keywords

Apoptosis; Breast cancer; ER stress; PI3K; VPS34-IN1.

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